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Archive - Jul 2009

Date

July 31st

Health Benefits of Red Wine May Aid Treatment of Inflammatory Diseases

Scientists have unraveled the mystery of how the red wine ingredient resveratrol is able to control inflammation. In this study, researchers administered an inflammatory agent to two groups of mice. One group was pretreated with resveratrol and the other group was not. The mice that were not pretreated with resveratrol experienced a strong inflammatory response, simulating disease in humans, while the group pretreated with resveratrol was protected from the inflammation. The scientists then examined the tissues of the mice to determine exactly how resveratrol was able to protect the mice from inflammation. They found that resveratrol used a one-two punch to stop inflammation in the mice by preventing the body from creating two different molecules known to trigger inflammation, sphingosine kinase and phospholipase D. This finding suggests that resveratrol may be harnessable as a treatment for inflammatory diseases and may also lead to entirely new resveratrol-based drugs that are even more effective. This work was published in the August issue of The FASEB Journal. "The therapeutic potential of red wine has been bottled up for thousands of years," said Dr. Gerald Weissmann, Editor-in-Chief of the journal, "and now that scientists have uncorked its secrets, they find that studies of how resveratrol works can lead to new treatments for life-threatening inflammation." [Press release] [FASEB abstract]

July 30th

Nanoparticles with Diphtheria Toxin Gene Target Ovarian Cancer

Nanoparticles containing the gene for a diphtheria toxin suicide protein can effectively suppress ovarian tumor growth in mice, according to a team of researchers from MIT and collaborating institutions. The findings could lead to a new treatment for ovarian cancer, which now causes more than 15,000 deaths each year in the United States. Because it is usually diagnosed at a relatively late stage, ovarian cancer is one of the deadliest forms of cancer. Currently, ovarian cancer patients undergo surgery followed by chemotherapy. In many cases, the cancer returns after treatment, and there are no good therapies for recurring and advanced-stage tumors. The new nanoparticles are made with positively charged, biodegradable polymers known as poly(beta-amino esters). When mixed together, these polymers can spontaneously assemble with DNA to form nanoparticles. The polymer-DNA nanoparticle can deliver functional DNA when injected into or near the targeted tissue. The packaged diphtheria toxin gene produces a diphtheria toxin suicide protein which kills cells by disrupting their ability to manufacture proteins. This work is reported in the August 1 issue of Cancer Research. [Press release] [Cancer Research abstract]

July 29th

New Zealand Walking Bat Has Ancient Heritage

A bizarre New Zealand bat that is as much at home walking four-legged on the ground as winging through the air had an Australian ancestor 20 million years ago with the same rare ability, a new study has found. The discovery overturns a long-held held view that the agile walking and climbing skills of the lesser short-tailed bat--Mystacina tuberculata--evolved in the absence of any ground-dwelling mammal competitors or predators, says an international team of researchers led by Dr Suzanne Hand, a bat expert at the University of New South Wales, Sydney, Australia. Along with the American common vampire bat--Desmodus rotundus--the New Zealand bat is one of only two of 1,100 bat species worldwide that has a true four-legged walking gait when maneuvering on the ground. It uses its wings as forelegs. Its thumb and toe claws have a unique extra talon for extra grip, plus a system of adhesive, gecko-like grooves in the soft, deeply wrinkled soles of its feet. The team has found that other special muscle and bone adaptations were also present in one of its extinct rainforest-dwelling Australian ancestors, fossils of which have been found at the rich Riversleigh World Heritage Fossil Site in north-west Queensland, it says in a report published in the journal BMC Evolutionary Biology. "The lesser short-tailed bat seems to be the sole survivor of an ancient Australian lineage now found only in New Zealand," said Dr Hand. "This study shows that, contrary to existing hypotheses, bats are not overwhelmingly absent from the ground because of competition from, or predation by, other mammals. Competition with other mammals and pressure from terrestrial predators does not deter modern vampire bats from walking.

July 28th

Researcher Recommend Two Genes for Barcoding of Plants

An international team of researchers has recommended using two genes for the barcoding of land plant, a step the team hopes will lead to a universal system for identifying over 400,000 species, and ultimately boost conservation efforts. Limiting the barcode to information generated from two DNA sites should help cut costs associated with sequencing and retrieving the correct information. "We've selected areas of DNA that are available in the vast majority of plants, could easily and accurately be sequenced, and when combined, provide a near-unique signature for barcoding,” said Dr. Sean Graham, an author of the study." The team selected two chloroplast genes referred to as rbcL and matK as the best candidates from which to generate barcode data. "There's no doubt this will be refined in the future, but there is a need for a core barcoding standard now," said Dr. Graham. "Particular research projects with special needs could augment the system by adding a third DNA locus to their barcode if required.” Barcodes based on portions of DNA--the taxonomical equivalent to UPC barcodes on products--have already emerged as a viable solution for uniquely identifying species in many animal groups. However, because DNA varies less between plant species, determining which portions of plant DNA to use as a unique identifier has been a thorny issue. This new work was published in PNAS the week of July 27. [Press release 1] [Press release 2] [PNAS abstract]

July 23rd

Androgen Receptors Are Reprogrammed in Lethal Stage of Prostate Cancer

A recent study reveals how late-stage, hormone-independent prostate tumors gain the ability to grow without the need of hormones. The onset of hormone-independent growth marks an advanced and currently incurable stage of prostate cancer, which is the most frequently diagnosed cancer in men. The study focused on androgen receptors, molecules located in the nuclei of cells of the prostate gland and other tissues. Male sex hormones—androgens--bind to these receptors to activate genes that control cell growth by regulating an early phase of the cell cycle. The researchers showed that in androgen-independent prostate cancer, androgen receptors are reprogrammed to regulate a group of genes involved in the later, mitotic phase of the cell cycle, triggering rapid cell growth. They further showed that an epigenetic modification associated with the UBE2C gene is involved in this reprogramming and that overexpression of this gene is necessary for the growth of the hormone-independent prostate cancer cells. These findings provide a better understanding of prostate cancer and could identify new therapeutic targets and lead to new treatments for the lethal, hormone-independent stage of the disease, said lead author Dr. Qianben Wang. Conducted by researchers at the Dana Farber Cancer Institute, Harvard Medical School, and collaborating institutions, this study was reported as a featured article in the July 24 issue of Cell. [Press release] [Cell article]

July 22nd

Gene Linked to Restless Legs Syndrome

Researchers at the Mayo Clinic, together with collaborators, have identified what is believed to be the first gene mutation linked to restless legs syndrome. The scientists identified the mutation (in the MEIS1 gene) in a family with six members. Three who had restless legs syndrome had the mutation and the other three without the disease did not. "The presence of the mutation in all affected individuals supports a pathogenic role for the MEIS1 gene, and we now need to confirm this finding with other international research groups who study restless legs syndrome," said Dr. Carles Vilariño-Güell, the lead author of the study. "The mutation we found is in a portion of the protein that is identical in species as distinct to human as frogs and fish, which tells us that this portion is very important for the proper function of the protein and that the mutation has a very high chance of causing disease," he said. The researchers doubt that a large proportion of the millions of people who suffer from the syndrome have this mutated MEIS1 gene. They point out, however, that understanding the function of both the normal gene and the abnormal gene will likely provide some insights into this mysterious disorder. Restless legs syndrome is estimated to affect between 5 and 11 percent of the population in Europe and in North America. The condition is characterized by unpleasant sensations in the legs at rest, especially in the evening, that are temporarily relieved by movement. Because restless legs syndrome often interrupts sleep, people commonly are diagnosed after they consult a sleep specialist for assistance. This research was reported in the July 21 issue of Neurology.

Wild Chimpanzees Can Die from AIDS-Like Illness

Although the AIDS virus entered the human population via chimpanzees, scientists have long believed that chimpanzees do not develop AIDS. Now, however, an international team of researchers, including Dr. Jane Goodall, has shown that wild chimpanzees infected with simian immunodeficiency virus (SIV) (the precursor of HIV-1) can, in fact, contract and die from an AIDS-like illness. The authors report that infected chimpanzees in their study group were 10-16 times more likely to die than those that were uninfected. The team also found that infected females were less likely to give birth and infants born to infected mothers were unlikely to survive. The virus, the researchers learned, was transmitted sexually and through mother's milk. Examination of tissue samples from dead chimpanzees revealed a loss of CD4+ T-cells (which are vital to immunity) in SIV-infected chimpanzees. Loss of these cells renders victims susceptible to many other infections--the classic indication of AIDS. “We hope this will lead to a better understanding of the virus that will benefit both humans and chimpanzees," commented Dr. Goodall. Dr. Beatrice Hahn was the senior author of this report, which appeared in the July 23 issue of Nature. [Press release 1] [Press release 2] [Nature News] [Nature abstract]

July 21st

Sea Lamprey Jettisons One-Fifth of Its DNA During Development

Early in embryonic development, the sea lamprey discards 20 percent of its DNA and dramatically remodels its genome. This remarkable finding was reported by researchers at the University of Washington and the Benaroya Research Institute. This is believed to be the first recorded observation of a vertebrate extensively reorganizing its genome as a normal part of development. The sea lamprey is a primitive fish that emerged from jawless fish first appearing 500 million years ago. It is essentially a living fossil from around the time that vertebrates originated. Sea lampreys have a long juvenile life as larvae in fresh water, where they eat on their own. Their short adult lives are normally spent in the sea as blood-sucking parasites. Their round, jawless mouths stick like suction cups to other fish. Several circular rows of teeth rasp through the skin of their unlucky hosts. Their appetite is voracious. Later, as they return to streams and rivers along the northern Atlantic seaboard, sea lampreys atrophy until they are little more than vehicles for reproduction. After mating, they perish. The scientists don't know how the lamprey’s large-scale genome reorganization happens, or why. The lead author said that his favorite hypothesis, yet unproven, is that the extra genetic material might play a role in the proliferation of precursor cells for sperm and eggs, and in early embryonic development. The genetic material might then be discarded either when it is no longer needed or to prevent abnormal growth. This work was reported in the July 7 issue of PNAS. [Press release] [PNAS abstract]

Drug-Dispensing Contact Lens Developed

Taking eye drops multiple times a day can be difficult to do, and, because of blinking and tearing, as little as 1 to 7 percent of the dose is actually absorbed by the eye. Now, researchers at Children’s Hospital Boston and collaborating institutions have developed a special contact lens that can gradually dispense a constant amount of medication to the eye, at adjustable rates. In laboratory testing, the prototype lens dispensed ciprofloxacin (an antibiotic often used in eye drops) for 30 days, the longest duration for which contact lenses are currently approved by the FDA; in some tests, the lens continued releasing drug for up to 100 days. The amounts dispensed were sufficient to kill pathogens in a laboratory assay. The researchers see applications in conditions such as glaucoma and dry-eye which require frequent daily eye drops. They have begun to test the prototype lens in animals and plan to begin human testing as soon as possible. The technology recently won the Life Sciences track in MIT's 100K Entrepreneurship Competition. This work was reported in the July issue of Investigative Ophthalmology and Visual Science. [Press release] [IOVS abstract]

July 20th

Puzzle Solution Points to Possible Treatment for Aggressive Alzheimer’s Disease

The puzzling behavior of a key enzyme has been explained and this may pave the way toward a possible treatment for a rapidly progressing form of Alzheimer’s disease (AD). Butyrylcholinesterase (BChE) breaks down the neurotransmitter acetylcholine and is associated with the neurofibrillary tangles and amyloid plaques that characterize AD. People with a particular mutation of the BChE gene, called the BChE-K mutation, are prone to more rapid development of AD than are those with the normal gene. This has been a puzzle because, in theory, the carriers of the mutated gene should be more protected from the devastating effects of the disease, because the mutated BChE breaks down acetylcholine at a slower rate than does the normal BChE. The result is that the mutation carriers maintain higher levels of this neurotransmitter, so they should, in principle, be protected from AD, in which acetylcholine levels decrease. In the current work, researchers at the Hebrew University of Jerusalem, and collaborating institutions, found that the mutation in the BChE-K gene damages the very end, or tail, of the resultant mutant protein. This tail is the part of BChE which is important for protection from the AD plaques. The tail does this by interacting with the AD beta-amyloid protein and preventing it from precipitating and forming the AD plaques. Thus, it seems that the K mutation can be both neuroprotective by sustaining acetylcholine levels and neurodegenerative by inefficiently interfering with the formation of AD plaques. To compare the normal protein to the K mutant, the researchers used synthetic tails of the normal and the K proteins, as well as engineered human BChE produced in the milk of transgenic goats. The goat-produced protein is prepared for the U.S. military as protection from nerve gas poisoning.